1286 - Reanalysis of the efficacy of molecular targeted agents (MTAs) given in the randomized trial SHIVA01 according to the ESMO ESCAT scale of actionability

Background

SIVHA01 was the first randomized precision medicine trial in patients (pts) with metastatic solid tumors comparing the efficacy of matched MTA outside their indications and conventional chemotherapy in pts with any kind of cancer who had failed standard of care therapy (Le Tourneau et al., Lancet Oncol 2015). No statistical difference was reported between the 2 groups in terms of progression-free survival (PFS), challenging the treatment algorithm used. Several scales of actionability have been developed to address this point, the latest one being the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) that defines clinical evidence-based criteria to prioritize genomic alterations to select MTAs for pts (Mateo et al., Ann Oncol 2018). We aimed to retrospectively evaluate the efficacy of MTAs given in SHIVA01 according to ESCAT.

Methods

All SHIVA01 molecular alterations targeted were ranked according to ESCAT by assessing the level of evidence reported in the literature, taking into account the tumor type and the administered MTA among 11. PFS and overall survival (OS) according to the ESCAT rank were compared using a log-rank test.All SHIVA01 molecular alterations targeted were ranked according to ESCAT by assessing the level of evidence reported in the literature, taking into account the tumor type and the administered MTA among 11. PFS and overall survival (OS) according to the ESCAT rank were compared using a log-rank test.

Results

The 153 pts treated with a MTA in SHIVA01 were included. Molecular alterations were ranked as II, IIIA, IIIB, and IVA according to ESCAT in 38 (25%), 98 (64%), 7 (5%), and 10 pts (7%), respectively. Median PFS was 2.0 months (mo) in tier II, 3.1 mo in IIIA; 1.7 mo in IIIB, and 3.2 mo in IVA (p = 0.13). Median OS was 11.7 mo in tier II, 11.2 mo in IIIA, 6.3 mo in IIIB, and 12.1 mo in IVA (p = 0.002).

Conclusions

The majority of molecular alterations taken into account in SHIVA01 were tier IIIA hypothetical targets according to ESCAT. Pts with a tier IIIB molecular alteration had the worst survival, highlighting the crucial impact of the types of molecular alterations beyond the gene and the signaling pathway.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Institut Curie.

Funding

ANR-10-EQPX-03 from the Agence Nationale de le Recherche (Investissements d’avenir) and SiRIC (Site de Recherche Intégré contre le Cancer).

Disclosure

All authors have declared no conflicts of interest.